Tegobuvir
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
Tegobuvir(TGV)是一种针对HCV RNA复制的非核苷类抑制剂,针对基因型1的EC50值小于16 nM,而对其他基因型的EC50值大于100 nM[1,2]。
Tegobuvir通过靶向NS5B聚合酶,抑制HCV的复制。NS5B聚合酶是RNA依赖性的RNA聚合酶,主要负责HCV复制[3,4]。HCV NS5B包含规范的拇指、手指和手掌区域[3]。
在体外HCV复制子中,Tegobuvir对基因型1a和1b的HCV病毒具有有效的活性,在HCV基因型1感染的患者和GT 1a中,EC50比GT 1b中高17倍[5]。然而,tegobuvir对GT2a复制子和GT2a感染性病毒具有较低的活性。此外,tegobuvir对C445F突变的EC50值增加7.1倍[2]。以上数据表明,tegobuvir的机制与HCV NS5B相关。NS5B的不同突变,包括C316Y、C445F和Y452H的数据表明,tegobuvir的抑制效果是由于其与拇指亚结构域发夹区的相互作用[2]。但是,TGV的机理仍未明确界定。在重组的NS5B蛋白中,TGV对NS5B的酶活性没有任何抑制作用[5]。在抗病毒测定中,tegobuvir与CYP1A抑制剂联合使用时, TGV的抗病毒能力降低,表明在经历一个多步代谢激活途径后,TGV与NS5B聚合酶结合[5]。TGV的活性也与特定谷胱甘肽加合物相关 [5]。在HeLa细胞系中,除了亚型的差异,TGV对GT 1b 复制子的效力较低,EC50值小于10 nM。
使用tegobuvir对个别患者治疗8天,HCV RNA的中位数减少1.5 log10 IU/mL。但是,使用PEG-IFN和RBV同时处理,RVR(在第4周,HCV RNA<25 IU/mL)的速率增加[5]。
参考文献:
1. Zeuzem S, Andreone P, Pol S, Lawitz E, Diago M, Roberts S, Focaccia R, Younossi Z, Foster GR, Horban A et al: Telaprevir for retreatment of HCV infection. N Engl J Med 2011, 364(25):2417-2428.
2. Wong KA, Xu S, Martin R, Miller MD, Mo H: Tegobuvir (GS-9190) potency against HCV chimeric replicons derived from consensus NS5B sequences from genotypes 2b, 3a, 4a, 5a, and 6a. Virology 2012, 429(1):57-62.
3. Shih IH, Vliegen I, Peng B, Yang H, Hebner C, Paeshuyse J, Purstinger G, Fenaux M, Tian Y, Mabery E et al: Mechanistic characterization of GS-9190 (Tegobuvir), a novel nonnucleoside inhibitor of hepatitis C virus NS5B polymerase. Antimicrob Agents Chemother 2011, 55(9):4196-4203.
4. Behrens SE, Tomei L, De Francesco R: Identification and properties of the RNA-dependent RNA polymerase of hepatitis C virus. EMBO J 1996, 15(1):12-22.
5. Hebner CM, Han B, Brendza KM, Nash M, Sulfab M, Tian Y, Hung M, Fung W, Vivian RW, Trenkle J et al: The HCV non-nucleoside inhibitor Tegobuvir utilizes a novel mechanism of action to inhibit NS5B polymerase function. PLoS One 2012, 7(6):e39163.
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 517.4 |
Cas No. | 1000787-75-6 |
Formula | C25H14F7N5 |
Synonyms | GS-333126;GS-9190;GS333126;GS9190 |
Solubility | ≥24.95 mg/mL in DMSO; insoluble in H2O; ≥100 mg/mL in EtOH |
Chemical Name | 5-[[6-[2,4-bis(trifluoromethyl)phenyl]pyridazin-3-yl]methyl]-2-(2-fluorophenyl)imidazo[4,5-c]pyridine |
SDF | Download SDF |
Canonical SMILES | C1=CC=C(C(=C1)C2=NC3=CN(C=CC3=N2)CC4=NN=C(C=C4)C5=C(C=C(C=C5)C(F)(F)F)C(F)(F)F)F |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
质量控制和MSDS
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